Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA773792 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.
2021-10-25 | GSE186444 | GEO
Project description:Background and aimsBiliary atresia is a severe inflammatory and fibrosing cholangiopathy of neonates of unknown etiology. The onset of cholestasis at birth implies a prenatal onset of liver dysfunction. Our aim was to investigate the mechanisms linked to abnormal cholangiocyte development.Approach and resultsWe generated biliary organoids from liver biopsies of infants with biliary atresia and normal and diseased controls. Organoids emerged from biliary atresia livers and controls and grew as lumen-containing spheres with an epithelial lining of cytokeratin-19pos albuminneg SOX17neg cholangiocyte-like cells. Spheres had similar gross morphology in all three groups and expressed cholangiocyte-enriched genes. In biliary atresia, cholangiocyte-like cells lacked a basal positioning of the nucleus, expressed fewer developmental and functional markers, and displayed misorientation of cilia. They aberrantly expressed F-actin, β-catenin, and Ezrin, had low signals for the tight junction protein zonula occludens-1 (ZO-1), and displayed increased permeability as evidenced by a higher Rhodamine-123 (R123) signal inside organoids after verapamil treatment. Biliary atresia organoids had decreased expression of genes related to EGF signaling and FGF2 signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation (cytokeratin 7 and hepatocyte nuclear factor 1 homeobox B) and functional (somatostatin receptor 2, cystic fibrosis transmembrane conductance regulator [CFTR], aquaporin 1) markers, restored polarity with improved localization of F-actin, β-catenin and ZO-1, increased CFTR function, and decreased uptake of R123.ConclusionsOrganoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell-cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.
| S-EPMC9983428 | biostudies-literature
Project description:We report label-free quantification of xenobiotic metabolizing enzymes (XME), transporters, redox enzymes, proteases and nucleases in 25 human liver microsomal samples, taken from patients with biliary atresia. Nearly 3500 proteins were identified and quantified. These data can be used in physiologically based pharmacokinetic models to predict appropriate drug doses drugs used in biliary atresia patients.
2021-09-09 | PXD020974 | Pride
Project description:Gene expression profile of biliary atresia at time of Kasai portoenterostomy was evaluated by comparing gene expression profile in biliary atresia and controls (choledochocyst).
2023-08-29 | GSE200517 | GEO
Project description:To investigate gene expression profile of human liver MAIT cells from patients with biliary atresia, we isolated human liver MAIT cells from liver tissues of patients with biliary atresia and from adjacent non-tumor liver tissues of hepatoblastoma patients (as control) at the time of diagnosis, and subjected for bulk RNA sequencing.
2024-05-15 | GSE217466 | GEO
Project description:Mapping Disease Pathways for Biliary Atresia
| PRJNA1032979 | ENA
Project description:Mapping Disease Pathways for Biliary Atresia
| PRJNA1032978 | ENA
Project description:We investigated bile-acid induced gene expression patterns in regulatory T-cells, and applied those gene sets to gene expression profiles of liver samples obtained from children with biliary atresia and intrahepatic cholestasis. Patient subgroups identified using the regulatory T-cell gene sets were then assessed for association with two-year outcome in patients with biliary atresia.
2022-12-20 | GSE221346 | GEO
Project description:BACKGROUND: Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. METHODS: We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. RESULTS: Fourteen of 47 livers displayed prominent features of inflammation (N=9) or fibrosis (N=5), with the remainder showing similar levels of both simultaneously. Differential profiling of gene expression of the 14 livers displayed a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. CONCLUSION: Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes. Clinical and laboratory data and liver biopies were obtained from 47 infants at diagnosis of biliary atresia and every 3-6 month intervals until 2 years of age as part of a prospective, observational study of the Biliary Atresia Research Consortium. Liver biopsies underwent histological scoring and those specimens classified as inflammation or fibrosis were used to generate a group-specific gene expression profile. The profile was used to assign a molecular stages of inflammation or fibrosis to the entire cohort. Molecular groups were tested for biological plausibility using immunostaining to quantify hepatic inflammatory cells, and quantitative PCR to reproduce the expression of gene groups and the expression of collagen genes. They were also tested for clinical relevance by testing of association with indicators of liver function, complications of disease, and clinical outcome. This dataset is part of the TransQST collection.
2010-08-31 | E-GEOD-15235 | biostudies-arrayexpress
Project description:Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip® Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia. Gene expression profiling: Liver biopsy samples obtained from infantas with other causes of intrahepatic cholestasis were served as diseased control. Liver tissue obtained from deceased-donor children were served as normal control. A molecular signataure of biliary atresia at the time of diagnosis was identified by comparing hepatic gene expression profile from biliary atresia to those from diseased and normal controls. This dataset is part of the TransQST collection.
2013-06-01 | E-GEOD-46960 | biostudies-arrayexpress